É uma condição de desenvolvimento do olho em que um ou os dois olhos são menores do que o normal (microftalmia). Essa condição vem acompanhada de um coloboma, que é uma falha ou fenda em alguma parte da estrutura do olho.
Introdução
O que você precisa saber de cara
É uma condição de desenvolvimento do olho em que um ou os dois olhos são menores do que o normal (microftalmia). Essa condição vem acompanhada de um coloboma, que é uma falha ou fenda em alguma parte da estrutura do olho.
Escala de raridade
<1/50kMuito rara
1/20kRara
1/10kPouco freq.
1/5kIncomum
1/2k
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Sinais e sintomas
O que aparece no corpo e com que frequência cada sintoma acontece
Partes do corpo afetadas
+ 16 sintomas em outras categorias
Características mais comuns
Os sintomas variam de pessoa para pessoa. Abaixo estão as 50 características clínicas mais associadas, ordenadas por frequência.
Linha do tempo da pesquisa
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Genética e causas
O que está alterado no DNA e como passa nas famílias
Genes associados
16 genes identificados com associação a esta condição. Padrão de herança: Autosomal dominant, Autosomal recessive.
Transcription factor that forms a trimeric complex with OCT4 on DNA and controls the expression of a number of genes involved in embryonic development such as YES1, FGF4, UTF1 and ZFP206 (By similarity). Binds to the proximal enhancer region of NANOG (By similarity). Critical for early embryogenesis and for embryonic stem cell pluripotency (PubMed:18035408). Downstream SRRT target that mediates the promotion of neural stem cell self-renewal (By similarity). Keeps neural cells undifferentiated by
Nucleus speckleCytoplasmNucleus
Microphthalmia, syndromic, 3
A disease characterized by the rare association of malformations including uni- or bilateral anophthalmia or microphthalmia, and esophageal atresia with trachoesophageal fistula. Microphthalmia is a disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in association with syndromes that include non-ocular abnormalities.
DNA repair protein involved in DNA non-homologous end joining (NHEJ); it is required for double-strand break (DSB) repair and V(D)J recombination and is also involved in telomere maintenance (PubMed:16439204, PubMed:16439205, PubMed:17317666, PubMed:17470781, PubMed:17717001, PubMed:18158905, PubMed:18644470, PubMed:20558749, PubMed:26100018, PubMed:28369633). Plays a key role in NHEJ by promoting the ligation of various mismatched and non-cohesive ends (PubMed:17470781, PubMed:17717001, PubMed:
NucleusChromosome
Immunodeficiency 124, severe combined
A form of severe combined immunodeficiency (SCID), a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia and low or absent antibody levels. Patients with SCID present in infancy with recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T- cell development. IMD124 is characterized by a profound T- and B- lymphocytopenia associated with increased cellular sensitivity to ionizing radiation, shortened telomeres and premature senescence of hematopoietic stem cells, microcephaly and growth retardation. Some patients may manifest SCID with sensitivity to ionizing radiation without microcephaly and mild growth retardation, probably due to hypomorphic NHEJ1 variants.
Receptor for Wnt proteins (PubMed:10097073, PubMed:20530549, PubMed:26908622, PubMed:9054360). Functions in the canonical Wnt/beta-catenin signaling pathway. In vitro activates WNT2, WNT10B, WNT5A, but not WNT2B or WNT4 signaling (By similarity). In neurons, activation by WNT7A promotes formation of synapses (PubMed:20530549). May be involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues (Probable). Plays a rol
Cell membraneGolgi apparatus membraneSynapsePerikaryonCell projection, dendriteCell projection, axon
Microphthalmia/Coloboma 11
A form of colobomatous microphthalmia, a disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues. Ocular abnormalities like coloboma, opacities of the cornea and lens, scaring of the retina and choroid, and other abnormalities may also be present. Ocular colobomas are a set of malformations resulting from abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure). MCOPCB11 is an autosomal dominant form with incomplete penetrance.
Functions as a retinol transporter. Accepts all-trans retinol from the extracellular retinol-binding protein RBP4, facilitates retinol transport across the cell membrane, and then transfers retinol to the cytoplasmic retinol-binding protein RBP1 (PubMed:18316031, PubMed:22665496, PubMed:9452451). Retinol uptake is enhanced by LRAT, an enzyme that converts retinol to all-trans retinyl esters, the storage forms of vitamin A (PubMed:18316031, PubMed:22665496). Contributes to the activation of a sig
Cell membrane
Microphthalmia, syndromic, 9
A rare clinical entity including as main characteristics anophthalmia or severe microphthalmia, and pulmonary hypoplasia or aplasia. Microphthalmia is a disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in association with syndromes that include non-ocular abnormalities.
Activates EIF2AK2/PKR in the absence of double-stranded RNA (dsRNA), leading to phosphorylation of EIF2S1/EFI2-alpha and inhibition of translation and induction of apoptosis. Required for siRNA production by DICER1 and for subsequent siRNA-mediated post-transcriptional gene silencing. Does not seem to be required for processing of pre-miRNA to miRNA by DICER1. Promotes UBC9-p53/TP53 association and sumoylation and phosphorylation of p53/TP53 at 'Lys-386' at 'Ser-392' respectively and enhances it
Cytoplasm, perinuclear regionCytoplasm
Dystonia 16
An early-onset dystonia-parkinsonism disorder. Dystonia is defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYT16 patients have progressive, generalized dystonia with axial muscle involvement, oro-mandibular (sardonic smile) and laryngeal dystonia and, in some cases, parkinsonian features.
May be involved in eye development
Nucleus
Optic disk anomalies with retinal and/or macular dystrophy
An ocular disorder characterized by optic nerve dysplasia, optic disk anomalies, chorioretinal dystrophy and macular atrophy. Some patients have microphthalmia.
Growth factor involved in early embryonic development and adipose-tissue homeostasis. During embryogenesis controls formation of anterior visceral endoderm and mesoderm and the establishment of anterior-posterior identity through a receptor complex comprising the receptor ACVR1B and the coreceptor CRIPTO (By similarity). Regulates adipose-tissue homeostasis and energy balance under nutrient overload in part by signaling through the receptor complex based on ACVR1C and CRIPTO/Cripto (PubMed:21805
SecretedCytoplasm
Klippel-Feil syndrome 3, autosomal dominant
A skeletal disorder characterized by congenital fusion of cervical vertebrae. It is due to a failure in the normal segmentation of vertebrae during the early weeks of fetal development. The clinical triad consists of short neck, low posterior hairline, and limited neck movement.
Involved in neural development by regulating the establishment of proper connectivity within the nervous system. Acts in both pre- and postsynaptic neurons in the hippocampus to control the assembly of a precise topographic projection: required in both CA1 and subicular neurons for the precise targeting of proximal CA1 axons to distal subiculum, probably by promoting homophilic cell adhesion. Required for proper dendrite morphogenesis and axon targeting in the vertebrate visual system, thereby p
Cell membraneCell projection, axon
Microphthalmia/Coloboma 9
A disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues. Ocular abnormalities like opacities of the cornea and lens, scaring of the retina and choroid, and other abnormalities may also be present. Ocular colobomas are a set of malformations resulting from abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure).
ATP-dependent transporter that catalyzes the transport of a broad-spectrum of porphyrins from the cytoplasm to the extracellular space through the plasma membrane or into the vesicle lumen (PubMed:17661442, PubMed:23792964, PubMed:27507172, PubMed:33007128). May also function as an ATP-dependent importer of porphyrins from the cytoplasm into the mitochondria, in turn may participate in the de novo heme biosynthesis regulation and in the coordination of heme and iron homeostasis during phenylhydr
Cell membraneMitochondrion outer membraneEndoplasmic reticulum membraneGolgi apparatus membraneEndosome membraneLysosome membraneLate endosome membraneEarly endosome membraneSecreted, extracellular exosomeMitochondrionEndosome, multivesicular body membraneMelanosome membrane
Microphthalmia/Coloboma 7
A disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues. Ocular abnormalities like opacities of the cornea and lens, scaring of the retina and choroid, and other abnormalities may also be present. Ocular colobomas are a set of malformations resulting from abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure).
The C-terminal part of the sonic hedgehog protein precursor displays an autoproteolysis and a cholesterol transferase activity (By similarity). Both activities result in the cleavage of the full-length protein into two parts (ShhN and ShhC) followed by the covalent attachment of a cholesterol moiety to the C-terminal of the newly generated ShhN (By similarity). Both activities occur in the endoplasmic reticulum (By similarity). Once cleaved, ShhC is degraded in the endoplasmic reticulum (By simi
Endoplasmic reticulum membraneGolgi apparatus membraneSecretedCell membrane
Microphthalmia/Coloboma 5
A disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues. Ocular abnormalities like opacities of the cornea and lens, scaring of the retina and choroid, and other abnormalities may also be present. Ocular colobomas are a set of malformations resulting from abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure).
Protein-serine O-palmitoleoyltransferase that acts as a key regulator of the Wnt signaling pathway by mediating the attachment of palmitoleate, a 16-carbon monounsaturated fatty acid (C16:1(9Z)), to Wnt proteins. Serine palmitoleoylation of WNT proteins is required for efficient binding to frizzled receptors
Endoplasmic reticulum membrane
Focal dermal hypoplasia
A rare congenital ectomesodermal disorder characterized by a combination of skin defects, skeletal abnormalities, and ocular anomalies. Affected individuals have patchy dermal hypoplasia, often in a distribution pattern following the Blaschko lines, and areas of subcutaneous fat herniation or deposition of fat into the dermis. In addition, sparse and brittle hair, hypoplastic nails and papillomas have been described. Skeletal abnormalities usually comprise syndactyly, ectrodactyly, and brachydactyly, and in some cases osteopathia striata has been seen. Patients frequently have ocular anomalies, including microphthalmia/ anophthalmia, coloboma, pigmentary and vascularization defects of the retina. Dental abnormalities are often present.
Retinol-binding protein that mediates retinol transport in blood plasma (PubMed:5541771). Delivers retinol from the liver stores to the peripheral tissues (Probable). Transfers the bound all-trans retinol to STRA6, that then facilitates retinol transport across the cell membrane (PubMed:22665496)
Secreted
Retinal dystrophy, iris coloboma, and comedogenic acne syndrome
A disease characterized by retinal degeneration, ocular colobomas involving both the anterior and posterior segment, impaired night vision and loss of visual acuity. Additional characteristic features include developmental abnormalities and severe acne.
Catalyzes the NAD-dependent oxidation of aldehyde substrates, such as all-trans-retinal and all-trans-13,14-dihydroretinal, to their corresponding carboxylic acids, all-trans-retinoate and all-trans-13,14-dihydroretinoate, respectively (By similarity) (PubMed:27759097). High specificity for all-trans-retinal as substrate, can also accept acetaldehyde as substrate in vitro but with lower affinity (PubMed:27759097). Required for the biosynthesis of normal levels of retinoate in the embryonic ocula
Cytoplasm
Microphthalmia, isolated, 8
A disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues. Ocular abnormalities like opacities of the cornea and lens, scaring of the retina and choroid, and other abnormalities may also be present.
Acts as a transcriptional regulator through binding to DNA at the consensus sequence 5'-[TC]TAATT[AG][AG]-3' upstream of gene promoters (PubMed:27301076). Plays a significant role in the specification and morphogenesis of the sensory retina (By similarity). May play a role in specification of V2a interneurons during spinal cord development (By similarity). Mediates differentiation of V2a interneurons by repression of motor neuron gene transcription, via competitively binding to response elements
Nucleus
Microphthalmia, isolated, 2
A disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues. Ocular abnormalities like opacities of the cornea and lens, scaring of the retina and choroid, and other abnormalities may also be present.
Growth factor that controls proliferation and cellular differentiation in the retina and bone formation. Plays a key role in regulating apoptosis during retinal development. Establishes dorsal-ventral positional information in the retina and controls the formation of the retinotectal map (PubMed:23307924). Required for normal formation of bones and joints in the limbs, skull, digits and axial skeleton. Plays a key role in establishing boundaries between skeletal elements during development. Regu
Secreted
Klippel-Feil syndrome 1, autosomal dominant
A skeletal disorder characterized by congenital fusion of cervical vertebrae. It is due to a failure in the normal segmentation of vertebrae during the early weeks of fetal development. The clinical triad consists of short neck, low posterior hairline, and limited neck movement. Deafness is a feature in some cases and may be of sensorineural, conductive, or mixed type.
Transcription factor probably involved in the development of the brain and the sense organs. Can bind to the bicoid/BCD target sequence (BTS): 5'-TCTAATCCC-3'
Nucleus
Microphthalmia, syndromic, 5
Patients manifest unilateral or bilateral microphthalmia/clinical anophthalmia and variable additional features including pituitary dysfunction, coloboma, microcornea, cataract, retinal dystrophy, hypoplasia or agenesis of the optic nerve, agenesis of the corpus callosum, developmental delay, joint laxity, hypotonia, and seizures. Microphthalmia is a disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in association with syndromes that include non-ocular abnormalities.
Variantes genéticas (ClinVar)
315 variantes patogênicas registradas no ClinVar.
Classificação de variantes (ClinVar)
Distribuição de 18 variantes classificadas pelo ClinVar.
Vias biológicas (Reactome)
46 vias biológicas associadas aos genes desta condição.
Diagnóstico
Os sinais que médicos procuram e os exames que confirmam
Tratamento e manejo
Remédios, cuidados de apoio e o que precisa acompanhar
Onde tratar no SUS
Hospitais de referência no Brasil e o protocolo oficial do SUS (PCDT)
🇧🇷 Atendimento SUS — Microftalmia colobomatosa
Selecione um estado ou use sua localização para ver resultados.
Dados de DATASUS/CNES, SBGM, ABNeuro e Ministério da Saúde. Sempre confirme a disponibilidade diretamente com o estabelecimento.
Pesquisa ativa
Ensaios clínicos abertos e novidades científicas recentes
Pesquisa e ensaios clínicos
Nenhum ensaio clínico registrado para esta condição.
Publicações mais relevantes
Intragenic loss-of-function variants in transcription factors MAZ, FOXP1 and SIN3B in colobomatous microphthalmia.
Despite the identification of many genes involved in developmental eye phenotypes, a large percentage of families lack genetic diagnoses, suggesting novel mechanisms remain to be discovered. Large deletions of 16p11.2, 3p14 or 19p13.11 regions involving transcription factors MAZ, FOXP1 and SIN3B, correspondingly, along with other genes, have been previously reported in individuals with neurodevelopmental and variable other features, including ocular coloboma and/or microphthalmia; recently, intragenic variants in FOXP1 and SIN3B have also been shown to cause neurodevelopmental phenotypes, with developmental eye defects reported in a small number of individuals with FOXP1 variants. Through exome sequencing analysis we identified novel splicing variants in MAZ and SIN3B, and a recurrent nonsense allele in FOXP1 in unrelated families affected with colobomatous microphthalmia, all with predicted loss-of-function effects; additionally, we report two new families with coloboma and 16p11.2 genomic deletions including MAZ, one de novo and another inherited from an affected parent. These findings provide further support for a role for FOXP1 in structural eye phenotypes, expanding its spectrum to include colobomatous microphthalmia, and suggest a role for MAZ and SIN3B in human eye development and disease.
Variants in NR6A1 cause a novel oculo vertebral renal syndrome.
Colobomatous microphthalmia is a potentially blinding congenital ocular malformation that can present either in isolation or together with other syndromic features. Despite a strong genetic component to disease, many cases lack a molecular diagnosis. We describe an autosomal dominant oculo-vertebral-renal (OVR) syndrome in six independent families characterized by colobomatous microphthalmia, missing vertebrae and congenital kidney abnormalities. Genome sequencing identified six rare variants in the orphan nuclear receptor gene NR6A1 in these families. We performed in silico, cellular, and zebrafish experiments to demonstrate the NR6A1 variants were pathogenic or likely pathogenic for OVR syndrome. Knockdown of either or both zebrafish paralogs of NR6A1 results in abnormal eye, kidney, and somite development, which was rescued by wild-type but not variant NR6A1 mRNA. Illustrating the power of genomic ascertainment in medicine, our study establishes NR6A1 as a critical factor in eye, kidney, and vertebral development, and a pleiotropic gene responsible for OVR syndrome.
Cataract Surgery in Congenital Colobomatous Microphthalmia Associated With Intraorbital Cyst in an Adult.
We report a challenging congenital cataract surgery in an adult case of colobomatous microphthalmia associated with intraorbital cyst.
The Arg99Gln Substitution in HNRNPC Is Associated with a Distinctive Clinical Phenotype Characterized by Facial Dysmorphism and Ocular and Cochlear Anomalies.
Background/Objectives: Heterozygous variants in the heterogeneous nuclear ribonucleoprotein C gene (HNRNPC) have recently been reported to cause intellectual developmental disorder-74 (MRD74), a neurodevelopmental disorder with no recurrent diagnostic handles. Affected individuals show variable, non-specific, and subtle dysmorphic features. The degree of developmental delay (DD)/intellectual disability (ID) is also wide, ranging from mild to severe. The mutational spectrum is relatively broad with exon deletions and splice site and frameshift variants distributed along the entire length of the gene leading to HNRNPC loss of function. Only two missense changes located within the RNA-binding motif (RBM) and adjacent linker region of the more abundant isoform (Arg64Trp and Arg99Gln) have been described. Notably, the Arg99Gln amino acid substitution was reported in a subject presenting with a more complex and unique clinical phenotype characterized by distinctive facial features, DD/ID, cochlear aplasia, and bilateral colobomatous microphthalmia, suggesting the possible occurrence of phenotypic heterogeneity. Results: Here, we report the second individual carrying the Arg99Gln change in HNRNPC and having clinical features with a significant overlap with the peculiar phenotype of the previously described subject, supporting the occurrence of a genotype-phenotype correlation. Conclusions: Due to the concomitant occurrence of ocular and cochlear involvement as recognizable diagnostic handles, we propose that the HNRNPCArg99Gln-related phenotype should be considered as a potential differential diagnosis in subjects with ID and major signs of CHARGE syndrome not fulfilling the minimum criteria for a clinical diagnosis.
[Bilateral colobomatous microphthalmia with unilateral orbital cyst].
Publicações recentes
Intragenic loss-of-function variants in transcription factors MAZ, FOXP1 and SIN3B in colobomatous microphthalmia.
Cataract Surgery in Congenital Colobomatous Microphthalmia Associated With Intraorbital Cyst in an Adult.
Variants in NR6A1 cause a novel oculo vertebral renal syndrome.
The Arg99Gln Substitution in HNRNPC Is Associated with a Distinctive Clinical Phenotype Characterized by Facial Dysmorphism and Ocular and Cochlear Anomalies.
Variants in NR6A1 cause a novel oculo-vertebral-renal (OVR) syndrome.
📚 EuropePMC22 artigos no totalmostrando 14
Intragenic loss-of-function variants in transcription factors MAZ, FOXP1 and SIN3B in colobomatous microphthalmia.
Journal of medical geneticsCataract Surgery in Congenital Colobomatous Microphthalmia Associated With Intraorbital Cyst in an Adult.
Case reports in ophthalmological medicineVariants in NR6A1 cause a novel oculo vertebral renal syndrome.
Nature communicationsThe Arg99Gln Substitution in HNRNPC Is Associated with a Distinctive Clinical Phenotype Characterized by Facial Dysmorphism and Ocular and Cochlear Anomalies.
GenesVariants in NR6A1 cause a novel oculo-vertebral-renal (OVR) syndrome.
Research square[Bilateral colobomatous microphthalmia with unilateral orbital cyst].
Journal francais d'ophtalmologieDe novo frameshift mutation in YAP1 associated with bilateral uveal coloboma and microphthalmia.
Ophthalmic geneticsNovel mutation in TENM3 gene in an Iranian patient with colobomatous microphthalmia.
Clinical case reportsCompound heterozygous splicing CDON variants result in isolated ocular coloboma.
Clinical geneticsHomozygous frameshift mutations in FAT1 cause a syndrome characterized by colobomatous-microphthalmia, ptosis, nephropathy and syndactyly.
Nature communicationsSequence variations in TENM3 gene causing eye anomalies with intellectual disability: Expanding the phenotypic spectrum.
European journal of medical geneticsA Case of Anterior Segment Dysgenesis with Iridolenticular Adhesions in Trisomy 18.
Journal of pediatric geneticsConfirmation of TENM3 involvement in autosomal recessive colobomatous microphthalmia.
American journal of medical genetics. Part ABosma arhinia microphthalmia syndrome: Clinical report and review of the literature.
American journal of medical genetics. Part AAssociações
Organizações que acompanham esta doença — pra ter apoio e orientação
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Comunidades
Grupos ativos de quem convive com esta doença aqui no Raras
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Referências e fontes
Bases de dados externas citadas neste artigo
Publicações científicas
Artigos indexados no PubMed ligados a esta doença no grafo RarasNet — título, periódico e PMID direto da fonte, sem intermediação de IA.
- Intragenic loss-of-function variants in transcription factors MAZ, FOXP1 and SIN3B in colobomatous microphthalmia.
- Variants in NR6A1 cause a novel oculo vertebral renal syndrome.
- Cataract Surgery in Congenital Colobomatous Microphthalmia Associated With Intraorbital Cyst in an Adult.
- The Arg99Gln Substitution in HNRNPC Is Associated with a Distinctive Clinical Phenotype Characterized by Facial Dysmorphism and Ocular and Cochlear Anomalies.
- [Bilateral colobomatous microphthalmia with unilateral orbital cyst].
- Variants in NR6A1 cause a novel oculo-vertebral-renal (OVR) syndrome.
Bases de dados e fontes oficiais
Identificadores e referências canônicas usadas para montar este verbete.
- ORPHA:98938(Orphanet)
- MONDO:0000170(MONDO)
- GARD:3644(GARD (NIH))
- Variantes catalogadas(ClinVar)
- Busca completa no PubMed(PubMed)
- Q55999509(Wikidata)
Dados compilados pelo RarasNet a partir de fontes abertas (Orphanet, OMIM, MONDO, PubMed/EuropePMC, ClinicalTrials.gov, DATASUS, PCDT/MS). Este conteúdo é informativo e não substitui avaliação médica.
Conteúdo mantido por Agente Raras · Médicos e pesquisadores podem colaborar
